Most inbred strains of mice are unable to make an antibody response to poly (glu50-ala50) (CT) due to a genetic defect which affects T and not B cells. Some mice produce specific suppressor T cells and suppressor factors in response to CT challenge. This phenomenon is controlled by major histocompatibility complex (H-2) genes. Preliminary studies show that CT suppressor strains will respond to CT challenge when suppressor T cells are eliminated by cyclophosphamid (CY) pretreatment, indicating that these mice bear immune response (Ir) genes for CT. Mice of the B6.C-H-2bm12 (bm12) strain differ by only a putative single point mutation from the C57BL/6 GT nonresponder, nonsuppressor strain. We propose to determine the underlying cause of GT unresponsiveness in GT nonresponder, nonrepressor mice. To this end, we will develop purified helper T-cell lines (clones) from bm12 and from CY-treated, CT-primed, suppressor and nonsuppressor, nonresponder strains of mice. CT-specific helper T-cell lines (clones) will be derived from these mice in order to characterize their function, surface phenotype (i.e., H-2 antigens) and soluble products (factors). CT-specific helper factors will be extracted from CT-primed, CY-treated lymphoid cells, cloned helper T-cell lines and T hybridomas. We propose to characterize these factors functionally both in vivo and in vitro and immunochemically. B-cell hybridomas producing antibodies directed against helper T-cell/factor determinants will be constructed in order to help elucidate their biological function. We will also determine whether the helper factor bears idiotypic markers in common with anti-CT antibodies. This investigation should lead to a further understanding of the regulation of the immune system and the balance between help and suppression.